Methotrexate is cytotoxic to trophoblast and, in low doses, has minimal side effects. It is used to treat gestational trophoblastic neoplasia and ectopic pregnancy and has recently been shown to have similar effects on intrauterine trophoblast. A prior study suggested that methotrexate may successfully cause abortion of an early pregnancy without prostaglandin. To test this hypothesis, ten pregnant women at < or = 42 days gestation were treated with methotrexate 50 mg/m2 intramuscularly. Vaginal bleeding started 24 +/- 10 (mean +/- standard deviation) days after the injection and lasted 10 +/- 3 days. Methotrexate side effects occurred in 4 patients and were limited to the first 4 days after the injection. Methotrexate alone appears sufficient to abort a very early intrauterine pregnancy.